Background: Cancer patients are at risk for a variety of treatment-related, including neurotoxicity (NT). Manifestations of NT are both structural and functional in presentation, yet the association between the two is poorly defined. We performed a cross-sectional pilot study to explore the relationship between 1H-MRSI and NP functioning in cancer patients with or at risk for NT. Objective: To identify relationships between metabolite ratios determined by 1H-MRSI ratios and NP test scores as mechanisms to identify and evaluate NT in cancer patients. Design/Methods: MRI and 1H-MRSI were performed on 30 patients, ages 2.4 40.5 yrs (mean 12.7 yrs, median 10.5 yrs), using a multi-slice, multi-voxel technique on a 1.5 T magnet. Eligible patients had a brain tumor, received systemic high dose chemotherapy, intrathecal therapy or cranial radiation, or had clinical NT from cancer treatment. Diagnoses included CNS tumor (n=19), lymphoma (n=9), and sarcoma (n=2). NT symptoms were present in 22 patients at enrollment. Cho:NAA, NAA:Cr and Cho:Cr ratios were determined in 8 pre-determined sites without tumor involvement. A battery of age-appropriate NP tests were administered within one week of imaging. The data were analyzed using Spearman rank correlations. Results: Mean full-scale IQ (FSIQ) score was 93.5 (median 96.5, range 61 138). Mean Verbal IQ (VIQ) score was 95.2 (median 98.0, range 59 141). Both FSIQ and VIQ scores were significantly correlated with 1H-MRSI in the basal ganglia (p<0.05). Academic tests of reading and arithmetic were also correlated with 1H-MRSI in the basal ganglia (p < .05). Behavioral assessments of socialization skills, internalizing behaviors, and quality of life were correlated with 1H-MRSI in the centrum semiovale, frontal grey matter, basal ganglia and thalamus (all ps < .05). Measures of expressive language (p < .05) and visual processing speed (p < .05) correlated with 1H-MRSI in the occipital-parietal white matter. Associations between measures of memory and 1H-MRSI in the hippocampus were identified as trends but did not reach statistical significance. Conclusions: This pilot study is the first to assess the relationship between NP testing and 1H-MRSI in cancer patients. Results indicate that 1H-MRSI may be useful in detecting functional CNS toxicities in cancer patients, but conclusions are limited by small sample size and heterogeneous population. Additional longitudinal study of 1H-MRSI and NP functioning in a homogeneous population is needed to further characterize NT in cancer patients.